Extended Data Fig. 5: Drug effects on brown adipose tissue.
From: GLP-1R–GIPR–PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice
a–d, Relative expression of thermogenic genes in BAT of DIO mice treated once-daily via s.c. injections of GLP-1:GIP, GLP-1:GIP:Lani or vehicle for 12 days. n = 8 each group. 10 nmol kg−1. a, Peroxisome proliferator-activated receptor gamma coactivator-1α (Pgc1α). b, Uncoupling protein 1 (Ucp1). c, PR domain containing 16 (Prdm16). d, Cell death-inducing DFFA-like effector a (Cidea1). e–s, Drug effects on mitochondrial function in differentiated immortalized BAT primary cells. 100 nM. e, Acute effects on mitochondrial respiration. f, Chronic effects on mitochondrial respiration. g, Acute effects on proton production rate. h, Chronic effects on proton production rate. i, proton leak respiration. j, Coupling efficiency. k, Maximal substrate oxidation. l, cellular respiration. m, Mitochondrial respiration. n, Non-mitochondrial respiration. o, ATP-linked respiration. p, Glycolysis. q, Glycolytic proton production rate. r, Glycolytic ATP production. s, ATP production from oxidative phosphorylation. Data were analysed using one-way ANOVA with Bonferroni post hoc multiple-comparison test (a–d,j,o,p,s), two-way repeated-measures ANOVA (e,f,g,h), or Kruskall-Wallis test with uncorrected Dunns’s test (i,k–n,q,r). Data in panel e,g comprise n = 11 independently differentiated wells per group; data in panel f,h–s comprise n = 26 independently differentiated wells for Lani and n = 27 independently differentiated wells for all other groups. Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001. Exact P-values, n-values and detailed statistics are provided in Supplementary Tables 1 and 3 and the Data Source File.
